The effectiveness and safety of transdermal fentanyl (TDF) was recently examined in a study published by Clinical Rheumatology. In this study, the use of fentanyl patches was assessed for those osteoarthritis (OA) patients inadequately managed with lower potency opioids. An eight week open-label trial evaluating the efficacy of TDF to manage OA pain of the hip or knee was undertaken, with the endpoint taken as patient reported improvement in pain control across five categories. Other efficacy assessments included pain intensity (numeric scale), functionality (WOMAC -OA index), health related quality of life (HRQol, SF-36 scale) and global impression of change. At the end of eight weeks 65% of patients experienced a sustained improvement in pain management and approvimately 50% were managed at 25mcg/hr requiring less than 1.3 g of rescue paracetamol. TDF also resulted in an improvement in health related quality of life and functioning for such patients. The majority of adverse effects were mild to moderate in severity, including nausea and dizziness and headache. The outcomes of this study back the guidelines for use of opioids including TDF for a defined subset of OA patients.
Osteoarthritis is a leading cause of disability.1 The non-opioid treatments available, including paracetamol and NSAIDs, are limited both in terms of pain management and adverse effects profile.1
While paracetamol can be beneficial in mild or moderate pain more severe pain is poorly controlled by paracetamol and continuous use has been associated with hepatotoxicity.1
NSAIDs are a treatment option that are useful in more severe conditions, but are known to have a ceiling effect and, in the case of non-selective NSAIDs, a high risk of GI events.1
Opioids therefore have been considered for treatment of OA patients who experience moderate to severe pain due to their known efficacy in managing chronic non-cancer pain.1 Opioids have a predictable side effects profile and are considered well tolerated in continuous use.1 The American Pain Society has also approved opioids for use in OA when other medication has not provided a reasonable level of pain relief and quality of life is reduced.1
Although this study did not evaluate the placebo effect which is known to weigh into perception of pain relief, there is precedent for the efficacy of TDF in multiple pain types.1 A published placebo-controlled study which has shown the effectiveness of TDF in management of OA pain has also previously been undertaken.1
This study, conducted at rheumatology and clinical research centres in Canada, evaluated the use of TDF in 81 patients satisfying American College of Rheumatology (ACR) diagnostic criteria for OA of the hip or knee and ACR functional class > 2.1 Participants also had a moderate to severe pain score (5-10) in the hip or knee and pain control assessment of excellent to very poor.1
Subjects began the trial with TDF 25mcg/hr for three days. After this time titration by addition of one additional 25mcg/hr releasing patch was allowed at intervals of 72 hrs. Rescue paracetamol was allowed up to a total of 4g/day and laxatives and antiemetics were administered according to standard opioid protocols during the first week and thereafter on an as needed basis.
Patients reported treatment outcomes at baseline, days 3, 6, 9, 14, 28, and at the conclusion of the trial. As a result of this study, 75% of patients reported an improvement in pain control by day 14 and 65% of patients reported that their pain was still well controlled at eight weeks.1
The mean reduction in pain intensity was 29%, representing a clinically measurable change, and 58% reported moderate to excellent pain control.1 The WOMAC score was rated as a clinically important change (> 20%) for over half the participants at eight weeks.1 HRQoL improvements were reported as statistically significant across the four measured categories and the global impression of change rating was improved in 55% of patients.1
At the end of treatment, 49% of patients had experienced adequate pain control with the 25mcg/hr patch and the mean daily dose of paracetamol required was 1.2 g/day.1
With regards to the efficacy of transdermal delivery compared to oral administration; previous studies have demonstrated TDF to achieve better pain control and quality of life in chronic non-cancer pain than other strong opioids.2 This may arise from the fact that after the initial 24 hr treatment period, plasma levels of fentanyl remain essentially constant.3 A constant steady-state plasma level of drug thus may represent an improvement in pain control compared to oral opioids, including sustained release morphine.2,3 Patient preference for TDF over oral sustained release morphine has been shown in randomised cross-over trials for chronic non-cancer pain.2
The adverse effects reported were in keeping with those reported for strong opioids: rated as mild to moderate and not of significant concern for most patients.1 These effects occurred at usual rates except constipation which was low at 21% but has been reported in other TDF studies.1,3
Overall TDF resulted in an improvement in pain management, HRQoL and functioning for this cohort of patients.1 The use of TDF as per current recommendations is supported for OA pain not managed with weak opioids.1
- Choquette D, McCarthy T, Rodrigues J et al. Transdermal fentanyl improves pain and functionality in patients with osteoarthritis: an open label Canadian trial. Clinical Rheumatology 2007.
- Walling A. Transdermal fentanyl vs. sustained-release morphine. American Family Physician 2002; 65(2): 291.
- Muijsers R, Wagstaff A. Transdermal fentanyl: an updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control. Drugs 2001; 61(15): 2289-307.